SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron
Abstract
La variante Omicron del SARS-CoV-2 tiene múltiples mutaciones de la proteína Spike (S) que contribuyen a escapar de las respuestas de anticuerpos neutralizantes y a reducir la protección de la vacuna frente a la infección. Se desconoce hasta qué punto otros componentes de la respuesta adaptativa, como las células T, pueden seguir dirigiéndose a Omicron y contribuir a la protección frente a resultados graves. Evaluamos la capacidad de las células T para reaccionar con el pico de Omicron en los participantes que fueron vacunados con Ad26.CoV2.S o BNT162b2, y en los pacientes convalecientes de COVID-19 no vacunados (n = 70). Encontramos que el 70-80% de la respuesta de las células T CD4 y CD8 a la espiga se mantuvo en todos los grupos del estudio. Además, la magnitud de las células T de reacción cruzada de Omicron fue similar a la de las variantes Beta y Delta, a pesar de que Omicron alberga considerablemente más mutaciones. Además, en los pacientes hospitalizados infectados por Omicron (n = 19), hubo respuestas de células T a la espiga ancestral, a la nucleocápside y a las proteínas de membrana comparables a las encontradas en pacientes hospitalizados en oleadas anteriores dominadas por las variantes ancestral, Beta o Delta (n = 49). Estos resultados demuestran que, a pesar de las extensas mutaciones de Omicron y la reducida susceptibilidad a los anticuerpos neutralizantes, la mayoría de la respuesta de las células T, inducida por la vacunación o la infección natural, reconoce la variante. Es probable que la inmunidad de células T bien conservada frente a Omicron contribuya a la protección frente a la COVID-19 grave, lo que respalda las primeras observaciones clínicas de Sudáfrica.
Competing Interest Statement
A. Sette is a consultant for Gritstone Bio, Flow Pharma, Arcturus Therapeutics, ImmunoScape, CellCarta, Avalia, Moderna, Fortress and Repertoire. All of the other authors declare no competing interests. LJI has filed for patent protection for various aspects of vaccine design and identification of specific epitopes.
Funding Statement
Research reported in this publication was supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation, including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also supported by the Poliomyelitis Research Foundation (21/65) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust (203135/Z/16/Z and 222574). This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.S. and Contract No. 75N9301900065 to A.S, D.W. P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (NRF; Grant No 9834). W.A.B. and C.R. are supported by the EDCTP2 programme of the European Union's Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to W.A.B.). N.A.B.N acknowledges funding from the SA-MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. A.S. acknowledges funding from the Bill and Melinda Gates award INV-018944, the NIH (AI138546) and the South African Medical Research Council. R.J.W. acknowledges funding from the Francis Crick Institute, which receives funding from Wellcome FC0010218, UKRI FC0010218 and CRUK FC0010218 and the Rosetrees Trust grant M926 (to C.R. and R.J.W.). For the purposes of open access, the authors have applied a CC-BY public copyright license to any author-accepted version arising from this submission.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The study was approved by the University of Cape Town Human Research Ethics Committee (ref: HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (ref. M210429 and M210752), the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (ref.BREC/00001275/2020) and the University of Pretoria Health Sciences Research Ethics Committee (ref. 247/2020).
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
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Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv
Hemos visto muchos errores. El mas obvio ha sido pensar que toda la respuesta inmunitaria (RI) vacunal o natural se centra en la presencia de Ac. Soy profesor de inmunología y se que la parte mas sencilla y mejor domina la gente son los Ac. Pero eso no los convierte ni en la única herramienta y ni siquiera en la mas importante. Se ha confundido comprensión y/o conocimientos individuales con certeza
El papel de las células T y la respuesta de memoria ha sido han sido los grandes olvidados. Desde diferentes (pocos) foros se ha reclamado su importancia, pero parecía un grito en el desierto. Se ha menospreciado por desconocimiento y eso ha hecho daño.
Lo peor es que esos gritos en el desierto se hacían con fundamento. Y no solo eso se defendía, ante la incredulidad de muchos, que gracias a esas respuestas celulares, las variantes no escaparían a las vacunas. Hace nada:
SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron
https://www.medrxiv.org/content/10.1101/2021.12.26.21268380v1
SARS-CoV-2 vaccination induces immunological memory able to cross-recognize variants from Alpha to Omicron
Abstract
We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, NVX-CoV2373) cross-recognize SARS-CoV-2 variants. Preservation of at least 83% and 85% for CD4+ and CD8+ T cell responses was found, respectively, regardless of vaccine platform or variants analyzed. By contrast, highly significant decreases were observed for memory B cell and neutralizing antibody recognition of variants. Bioinformatic analyses showed full conservation of 91% and 94% of class II and class I spike epitopes. For Omicron, 72% of class II and 86% of class I epitopes were fully conserved, and 84% and 85% of CD4+ and CD8+ T cell responses were preserved. In-depth epitope repertoire analysis showed a median of 11 and 10 spike epitopes recognized by CD4+ and CD8+ T cells from vaccinees. Functional preservation of the majority of the T cell responses may play an important role as a second-level defense against diverse variants.
Competing Interest Statement
A.S. is a consultant for Gritstone Bio, Flow Pharma, Arcturus Therapeutics, ImmunoScape, CellCarta, Avalia, Moderna, Fortress and Repertoire. SC has consulted for GSK, JP Morgan, Citi, Morgan Stanley, Avalia NZ, Nutcracker Therapeutics, University of California, California State Universities, United Airlines, and Roche. All of the other authors declare no competing interests. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work.
https://www.biorxiv.org/content/10.1101/2021.12.28.474333v1
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